Department of Surgery, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. m.koppe@chir.umcn.nl
Nov, 2006
Because tumor targeting with radiolabeled monoclonal antibodies is more efficient in small lesions, radioimmunotherapy is considered most suitable for minimal or microscopic residual disease. The aim of the present studies was to assess the efficacy of adjuvant radiommunotherapy using radiolabeled monoclonal antibodies after cytoreductive surgery in rats with peritoneal carcinomatosis of colonic origin.We used a tumor model, in which peritoneal carcinomatosis was induced by intraperitoneal inoculation of CC-531 colon carcinoma cells in Wag/Rij rats. The biodistribution of the (125)I-/(111)In-labeled anti-CC-531 MG1 monoclonal antibody after intraperitoneal administration was assessed. Subsequently, the efficacy of (177)Lu-MG1 (74 MBq per rat) was compared with that of unlabeled MG1 or phosphate-buffered saline-bovine serum albumin in this model. Finally, rats with resectable intraperitoneal CC-531 tumors were subjected to exploratory laparotomy only, cytoreductive surgery only, exploratory laparotomy + radiommunotherapy (56 MBq (177)Lu-MG1 per rat), or cytoreductive surgery + radiommunotherapy. Survival was the primary endpoint.Both (125)I- and (111)In-labeled MG1 preferentially accumulated in intraperitoneal CC-531 tumors. The uptake of (111)In-MG1 in tumor was higher than that of (125)I-MG1 (4.1 +/- 2.3 \%ID/g vs. 1.1 +/- 0.5 \%ID/g [\%ID/g is percentage of injected dose per gram], 72 h after injection; P = 0.053). Radiommunotherapy with 74 MBq (177)Lu-MG1 almost completely eradicated tumor growth, whereas unlabeled MG1 had no effect. In the surgery study, both cytoreductive surgery and radiommunotherapy were well tolerated. The median survival of the control rats that underwent exploratory laparotomy only was 41 d. The median survival of the rats that were treated with cytoreductive surgery only, exploratory laparotomy + radiommunotherapy, or cytoreductive surgery + radiommunotherapy was 51 d (P = 0.05 compared with control rats), 61.5 d (P = 0.03), and 88 d (P = 0.0001), respectively, which suggests an additive effect of both treatment modalities. There was a highly significant trend toward improved survival of cytoreductive surgery + radiommunotherapy compared with both monotherapies (P = 0.0004).This study provides proof of principle that radiommunotherapy can be an effective treatment modality when applied as an adjuvant treatment after resection of tumors with a high risk of recurrence, such as after cytoreductive surgery of peritoneal carcinomatosis.